The interaction of bacteria and the classical and alternative complement pathways and polymorphonuclear and mononuclear phagocytes will be studied in vitro in the following projects: (1) Function of the alternative complement pathway in defense against bacteria and the role of the spleen in that function. Hemolysis through the alternative pathway will be studied kinetically in serum from patients with sickle cell disease or previous splenectomy. The patient's experience with bacterial infection will be compared to the activity of his serum in the alternative pathway, and attempts will be made to identify factors deficient in abnormal sera. The requirements for and kinetics of hemolysis through the alternative pathway will be studied, in particular the role of antibody in this process. The role of C3b fixed to the particle in its binding to and ingestion by neutrophils will be analyzed. (2) The mechanism of bacterial killing in phagocytes. The relationship between superoxide anion, hydrogen peroxide, hydroxyl radical, and singlet oxygen and phagocytic bactericidal activity in polymorphonuclear leukocytes will be studied. The release of these agents upon stimulation by contact with surface-active agents or immune complexes, and the effect of anti-inflammatory drugs on this release will be explored. Attempts will be made to demonstrate hydroxyl radical release by phagocytizing neutrophils and to analyze the basic oxidative metabolic defect of chronic granulomatous disease. BIBLIOGRAPHIC REFERENCES: DeChatelet, L. R., Shirley, P. S., and Johnston, R. B., Jr.: Effect of phorbol myristate acetate on the oxidative metabolism of human polymorphonuclear leukocytes. Blood 47:545, 1976. Johnston, R. B., Jr., and Lehymeyer, J. E.: Elaboration of toxic oxygen by-products by neutrophils in a model of immune complex disease. J. Clin. Invest. 57:836, 1976.